The present project's goal is to develop oral medications for the treatments of atopic dermatitis, asthma and allergic rhinitis. SAR studies have produced two lead compounds that show increased potency and markedly reduced side affects compared with previously used drugs of this class. Notably, the two lead compounds are chiral due to atropisomerism. Though well precedented in physical organic chemistry, atropisomerism is a rather uncommon form of chirality exhibited by drugs or drug candidates, and adds a layer of complexity in developing these compounds. The present project's specific aims are: 1. To develop efficient methods to synthesize atropisomers (enantiomers) of the lead compounds in high chemical yields and in high enantiomeric excess. 2. To determine the physico-chemical properties of the atropisomers of the lead compounds so that the chiral stability can be ascertained, and so that optimal salt forms can be identified that ensure high ee in shelf life. 3. To study and contrast the metabolism of the atropisomers of the lead compounds in vitro and the pharmacokinetics and metabolism in vivo, to aid in selecting the optimal atropisomer of each compound for preclinical development.